Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

There were 90 enrolling sites in 15 countries. The first participant was screened on 09 June 2005, and the last participant was randomized on 15 June 2006. The last participant observation (LPO) for the primary endpoint analysis (Week 48) was 11 May 2007. The LPO for the Week 96 analysis was 27 May 2008.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

Six of the 272 participants who were successfully screened and randomized discontinued prior to the first dose of study drug due to being erroneously randomized via interactive voice response system, withdrawal of consent, loss to follow-up, or failure to meet screening criteria. The screening process involved a liver biopsy.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Randomized-and-treated analysis set. Based on Knodell numerical scoring of liver biopsy specimens. This scale consists of 5 domains (Periportal with or without Bridging Necrosis [scored numerically from best to worst 0, 1, 3, 4, 5, 6, or 10]; Intralobular Degeneration and Focal Necrosis [scored best to worst 0 to 4]; Portal Inflammation [also scored best to worst 0 to 4]; and Fibrosis [also scored best to worst 0 to 4]). The necroinflammatory score is the combined score for Necrosis and Inflammation, excluding the Fibrosis score. Scores may range from 0 (best) to 14 (worst).

Hepatitis B e-antigen (HBeAg) loss was defined as negative HBeAg result for those subjects with HBeAg-positive result at baseline. Seroconversion to anti-HBe was defined as HBeAg loss and positive anti-HBe result.

Time Frame

Week 48

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

HBeAg loss and seroconversion analysis was based upon the serologically evaluable analysis set, which consisted of all randomized-and-treated participants with a positive HBeAg result at baseline. Denominator used was the number of serologically evaluable participants.

Additional details about the analysis, such as null hypothesis and power calculation:

No text entered.

[2]

Details of power calculation, definition of non-inferiority margin, and other key parameters:

With a sample size of 160 subjects in the TDF group and 80 subjects in the ADV group, a two group large-sample normal approximation test of proportions with a one-sided 0.025 significance level would have 95% power to reject the null hypothesis that the TDF treatment was inferior to the ADV treatment (the difference in proportions was less than 0.080) in favor of the alternative hypothesis that the TDF treatment was not inferior.

[3]

Other relevant method information, such as adjustments or degrees of freedom:

No text entered.

[4]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

P-value above for HBeAg loss corresponds to a Z-test of the null hypothesis that stratum-adjusted difference is zero. Difference, standard error of the difference, and CI are stratum adjusted based on baseline ALT category (</= 4 x ULN or >4 x ULN).

Additional details about the analysis, such as null hypothesis and power calculation:

No text entered.

[2]

Details of power calculation, definition of non-inferiority margin, and other key parameters:

With a sample size of 160 subjects in the TDF group and 80 subjects in the ADV group, a two group large-sample normal approximation test of proportions with a one-sided 0.025 significance level would have 95% power to reject the null hypothesis that the TDF treatment was inferior to the ADV treatment (the difference in proportions was less than 0.080) in favor of the alternative hypothesis that the TDF treatment was not inferior.

[3]

Other relevant method information, such as adjustments or degrees of freedom: